Abstract：
:With the completion of the genome of Mycobacterium tuberculosis comes the promise of a new generation of potent drugs to combat the emerging epidemic of multiply drug-resistant isolates. Translating this genomic information into realistic assays, valid targets, and preclinical drug candidates represents the next great hope in tuberculosis control. We propose a paradigm for exploiting the genome to inform the development of novel antituberculars, utilizing the techniques of differential gene expression as monitored by DNA microarrays coupled with the emerging discipline of combinatorial chemistry. A comparison of currently used antituberculars with the properties of other pharmaceuticals suggests that such compounds will have a defined range of physiochemical properties. In general, we can expect the next generation of antituberculars to be small, relatively hydrophilic molecules that bind tightly to specific cellular targets. Many current antimycobacterials require some form of cellular activation (e.g. the activation of isoniazid by a catalase-peroxidase). Activation corresponds to the oxidative, reductive, or hydrolytic unmasking of reactive groups, which occurs with many current antimycobacterial prodrugs. Understanding the mechanisms involved in activation of current antimycobacterial therapeutics also may facilitate the development of alternative activation strategies or of analogs that require no such processes.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Barry CE 3rd,Slayden RA,Sampson AE,Lee REdoi
10.1016/s0006-2952(99)00253-1subject
Has Abstractpub_date
2000-02-01 00:00:00pages
221-31issue
3eissn
0006-2952issn
1873-2968pii
S0006-2952(99)00253-1journal_volume
59pub_type
杂志文章abstract：:Somatostatin receptors from rabbit retinal membranes were solubilized in an active form using a mixture of the detergent n-octyl b-D-glucopyranoside (OG) and CHAPS. The binding of [125I]-Try11-somatostatin to the soluble extract was saturable and of high affinity, with an apparent affinity constant (Kd) of 0.60 +/- 0....
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90439-4
更新日期：1993-05-05 00:00:00
abstract：:Adriamycin (ADR), a well-known antitumoral drug, interacts with DNA (nuclear and mitochondrial) and cardiolipin. Moreover, ADR induces numerous mitochondrial modifications in sensitive cells. However, no results have yet been obtained as to the repercussions of drug effects on oxido-reductase activities in ADR-resista...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00084-7
更新日期：1998-08-15 00:00:00
abstract：:Stimulated mast cells produce and release adenosine, and the release of mast cell mediators is potentiated by adenosine, yet very little is known regarding mast cell purine metabolism. Because 5-amino-4-imidazolecarboxamide riboside (AICA riboside) has been shown to alter adenosine metabolism and accelerate the replet...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90757-4
更新日期：1986-12-15 00:00:00
abstract：:Disodium cromoglycate and compounds which elevated levels of cyclic AMP in the mast cell variously inhibited cytotoxic histamine release induced by the surface active agents melittin, Tween 20 and Triton X-100. These results are inconsistent with the postulated effects of the drugs on receptor mediated calcium channel...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90109-5
更新日期：1982-07-01 00:00:00
abstract：:Entrectinib is a new tyrosine kinase inhibitor that was recently approved for the treatment of ROS1-positive metastatic non-small cell lung cancer (NSCLC). In this study, we aimed to characterize its potential to act as a modulator of pharmacokinetic cytostatic resistance and perpetrator of drug interactions. In accum...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114061
更新日期：2020-08-01 00:00:00
abstract：:The antitumor, DNA-alkylating agent 1,3-bis[2-chloroethyl]-2-nitrosourea (BCNU; Carmustine), which generates 2-chloroethyl isocyanate upon decomposition in situ, inhibits cellular glutathione reductase (GR; EC 1.8.1.7) activity by up to 90% at pharmacological doses. GR is susceptible to attack from exogenous electroph...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.02.016
更新日期：2005-05-15 00:00:00
abstract：:Escape from the proper control of the cell cycle by up-regulation of cyclins or aberrant activation of cyclin-dependent kinases (CDKs) as well as by inactivation of cellular inhibitors of CDKs (CKI) leads to malignant transformation. Loss of cellular CKIs in cancers provided a rationale for development of pharmacologi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.07.040
更新日期：2008-12-01 00:00:00
abstract：:The toxicity of the organophosphorus poison soman (pinacolylmethylphosphonofluoridate) is attributable to its irreversible inhibition of the enzyme acetylcholinesterase. In addition, soman binds irreversibly to a number of noncholinesterase tissue binding sites which appear to be its major means of in vivo detoxificat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90349-p
更新日期：1990-10-15 00:00:00
abstract：:A form of cytochrome P-450, P-450-D3, cross reactive with antibodies to rat P-450d was purified from liver microsomes of polychlorinated biphenyl (PCB)-treated female Beagle dogs to an electrophoretic homogeneity. Judging from the result of sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the molec...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90154-8
更新日期：1989-01-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00183-5
更新日期：1999-10-01 00:00:00
abstract：:The human P2Y₁₁ nucleotide receptor mRNA was found in virtually all human tissues, and the receptor serves many physiological roles, such as immune response regulation. The Ala-87-Thr-P2Y₁₁ receptor single nucleotide polymorphism was linked to increased risk for acute myocardial infarction. To facilitate the developme...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2013.06.013
更新日期：2013-09-01 00:00:00
abstract：:In this study we compared two methods, electron spin resonance (ESR) spectroscopy and high performance liquid chromatography (HPLC), which are currently used to detect directly hydroxyl radical (OH.) formation in the ischemic and reperfused heart. Isolated buffer-perfused rat hearts were subjected to 30 min of normoth...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90182-v
更新日期：1993-02-24 00:00:00
abstract：:As previously shown with isolated oxyhemoglobin, methemoglobin formation can also be induced in intact erythrocytes by hydroxylamine compounds and substituted phenols such as butylated hydroxyanisole (BHA). Electron spin resonance investigations revealed that, accordingly, free radical intermediates were formed in ery...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(96)00460-1
更新日期：1996-12-24 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90020-w
更新日期：1993-05-25 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90059-x
更新日期：1983-06-15 00:00:00
abstract：:Increasing evidence is accumulating that zoledronic acid (ZOL), a nitrogen-containing bisphosphonate (N-BP), is able to affect tumor cells by inhibiting the enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway (MVP). The consequent accumulation of unprenylated proteins is believed to largely account...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.10.003
更新日期：2010-03-01 00:00:00
abstract：:The mechanism of the antiaggregating activity of flavonoids was studied in vitro. The activity of fifteen different compounds was tested on platelet aggregation and arachidonic acid metabolism. The effect of flavonoids on platelet adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels under basal conditions, as well...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90423-4
更新日期：1984-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00823-1
更新日期：2001-12-15 00:00:00
abstract：:The effects of sulfobromophthalein (SBP) and ethacrynic acid (ECA), both inhibitors of glutathione S-transferase (GST), or glyceryl trinitrate (GTN)-induced vasorelaxation were investigated in rabbit aortic strips. The aortic strips were pre-contracted with phenylephrine, followed by relaxation with 0.5 microM GTN, wi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90184-k
更新日期：1992-05-28 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90275-x
更新日期：1989-03-15 00:00:00
abstract：:Intracellular cyclic AMP accumulation following exposure to dopamine (DA) agonists and and antagonists was measured in striatal slices from rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway and which showed contralateral circling to apomorphine. Both DA (10-320 microM) and the D-1 a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90040-p
更新日期：1992-07-07 00:00:00
abstract：:Previous reports have demonstrated that cadmium (Cd) may induce cell death via apoptosis, but the mechanism responsible for cellular death is not clear. In this study, we investigated the signaling pathways implicated in Cd-induced apoptosis in lung epithelial fibroblast (WI 38) cells. Apoptotic features were observed...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.06.021
更新日期：2004-11-01 00:00:00
abstract：:We examined the effects of the divalent cation calcium (Ca2+) and the monovalent cations potassium (K+) and sodium (Na+) and different modalities that affect the fluxes of these cations on immunoreactive secretin (IRS) secretion from canine duodenal mucosa in vitro. In the absence of extracellular Ca2+, the basal IRS ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90505-9
更新日期：1988-03-15 00:00:00
abstract：:Neuronal nicotinic acetylcholine receptors are expressed on a variety of cells in the nervous system where they play key roles in synaptic transmission and information transfer. Little is known, however, about the molecular mechanisms that control their expression, distribution, and function during nervous system deve...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02067-5
更新日期：1995-11-09 00:00:00
abstract：:5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) which are involved in inflammatory diseases and allergic reactions. The pathophysiological effects of LTs are considered to be prevented by 5-LO inhibitors. In this study we presen...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.10.012
更新日期：2012-01-15 00:00:00
abstract：:Increasing evidence supports NLRP3 inflammasome as a new target to control inflammation. Dysregulation of NLRP3 inflammasome has been reported to be involved in the pathogenesis of several human inflammatory diseases. However, no NLRP3 inflammasome inhibitors are available in clinic. Terpenoids are natural products wi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2019.113739
更新日期：2020-02-01 00:00:00
abstract：:We tested the influence of IFNgamma on proteasome activity in parental Hep G2 cells that do not metabolize ethanol, as well as in recombinant Hep G2-derived cells that express either or both alcohol dehydrogenase (ADH) and cytochrome P4502E1 (CYP2E1). IFNgamma treatment increased proteasome activity in VL-17A (ADH(+),...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00252-1
更新日期：2003-09-01 00:00:00
abstract：:Incubation of human carcinoma cells with mitoxantrone resulted in an intracellular distribution of the drug into cytoplasmic, nuclear and cytoskeletal compartments occurring within 1 min of drug treatment. Incubation of the cells in drug-free medium resulted in an efflux of the drug such that 80% of the intracellular ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90527-3
更新日期：1989-12-01 00:00:00
abstract：:Phospholipase A2 (PLA2) cleave phospholipids preferentially at the sn-2 position, liberating free fatty acids and lysophospholipids. They are classified into six main groups based on size, location, function, substrate specificity and calcium requirement. These classes include secretory PLA2 (sPLA2), cytosolic (cPLA2)...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2014.05.022
更新日期：2014-08-15 00:00:00
abstract：:Previous work has shown that 5-hydroxytryptamine (5-HT)2A receptors can be radiolabelled with various radioligands, including partial agonists, such as [125I]-DOI and [3H]-DOB, and antagonists, such as [3H]-ketanserin and [3H]-spiperone. Because 5-HT has high affinity for the 5-HT2A receptor when displacing [3H]-DOB, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02122-1
更新日期：1996-01-12 00:00:00
